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Introduction The low frequency of ectopic germinal center in labial salivary glands of patients with human T‐cell leukemia virus type 1 (HTLV‐1) antibody‐positive Sjögren's syndrome (SS) suggests that HTLV‐1 has some effects on follicular dendritic cells (FDCs). Methods We used flow cytometry, immunofluorescence, and enzyme‐linked immunosorbent assays (ELISAs) to investigate the direct effect of HTLV‐1 on B‐cell activating factors produced by established FDC like cells obtained from excised human tonsils. We then measured the serum B‐cell activating factor (BAFF) and C‐X‐C motif ligand (CXCL) 13 concentrations of the HTLV‐1‐seropositive SS patients and the HTLV‐1‐seronegative SS patients by ELISA. Results Among the 31 isolated specimens, 22 showed morphological characteristics of FDCs. Day 2‐cultured specimens showed expressions of CD14, CD23, CD40, intracellular adhesion molecule‐1 (ICAM‐1), and vascular cell adhesion molecule‐1. After 2 weeks, 12 of these specimens expressed ICAM‐1, FDC, and fibroblast cell marker. Intracellular BAFF and CXCL13 were constitutively expressed regardless of stimulation. After direct coculture with the HTLV‐1‐infected T‐cell line HCT‐5 or MT‐2, the BAFF and CXCL13 expressions on the FDC‐like cells were decreased in accord with the increased number of HCT‐5 and MT‐2 cells with styliform change and without HTLV‐1 Gag protein expression. Interferons upregulated the concentration of BAFF (but not CXCL13) in the culture supernatant, which showed a declining trend under the presence of HCT‐5 or MT‐2. The serum concentrations of BAFF and CXCL13 in the HTLV‐1‐seropositive SS patients were lower than those of the HTLV‐1 seronegative SS patients. Conclusions HTLV‐1 partially inhibited the BAFF and CXCL13 expressions of established FDC‐like cells., Graphical abstract Expression of B‐cell activating factor (BAFF) was upregulated by addition of interferons. Although BAFF expression was inhibited by addition of human T‐cell leukemia virus type 1 infected cell line, HCT‐5 and MT‐2, the level was not inhibited by addition of control cell line, MOLT‐4.

Introduction Neurogenic overactive bladder is a main feature of human T-cell leukemia virus type 1-associated myelopathy/tropical spastic paraparesis. We successfully performed intravesical onabotulinumtoxinA therapy for refractory neurogenic overactive bladder due to human T-cell leukemia virus type 1-associated myelopathy/tropical spastic paraparesis. Case presentation We retrospectively reviewed four neurogenic overactive bladder patients with human T-cell leukemia virus type 1-associated myelopathy/tropical spastic paraparesis who underwent bladder wall injections of onabotulinumtoxinA from April to October 2020. All patients were female. Their median age was 66 (range, 63-71) years. They were previously treated with β3-adrenergic receptor agonists or anticholinergic drugs alone or in combination for ≥12 weeks. However, insufficient results were obtained. After 4 weeks of intravesical onabotulinumtoxinA therapy, overactive bladder symptoms improved and maximum cystometric capacity increased in all cases. Conclusion Intravesical onabotulinumtoxinA therapy may be useful for treating refractory overactive bladder due to human T-cell leukemia virus type 1-associated myelopathy/tropical spastic paraparesis.

Objective: Major salivary gland ultrasonography (SGUS) is widely used for the diagnosis of primary Sjögren’s syndrome (pSS). Our objective was to assess the contribution of SGUS compared to other items of the 2016 ACR/EULAR pSS classification criteria, based on expert opinion. Methods: A secure web‐based relational database was used by 24 experts from 14 countries to assess 512 realistic vignettes developed from data of patients with suspected pSS. Each vignette provided classification criteria items and information on history, clinical symptoms and SGUS findings. Each expert assessed 64 vignettes, and each vignette was assessed by 3 experts. A diagnosis of pSS was defined according to at least 2 of 3 experts. Validation was performed in the independent French DiapSS cohort of patients with suspected pSS. Results: A criteria‐based pSS diagnosis and SGUS findings were independently associated with an expert diagnosis of pSS (P < 0.001). The derived diagnostic weights of individual items in the 2016 ACR/EULAR criteria including SGUS were as follows: anti‐SSA, 3; focus score ≥ 1, 3; SGUS score ≥ 2, 1; positive Schirmer’s test, 1; dry mouth, 1; and salivary flow rate < 0.1 mL/min, 1. The corrected C statistic area under the curve for the new weighted score was 0.96. Adding SGUS improves the sensitivity from 90.2 % to 95.6% with a quite similar specificity 84.1% versus 82.6%. Results were similar in the DiapSS cohort: adding SGUS improves the sensitivity from 87% to 93%. Conclusion: SGUS had similar weight compared to minor items, and its addition improves the performance of the 2016 ACR/EULAR classification criteria. acceptedVersion

子ども食堂は、地域で子どもたちの問題を共有する居場所としての意味合いが強い。長崎国際大学においても、2015年から子ども食堂の活動がスタートし、社会福祉学科と地域連携室を中心に活動を進めてきた。大学で子ども食堂を運営していくことは、学生が地域の課題に取り組むことで本人の成長の機会になる教育的な意味がある。そこで本研究では、2018年度の長崎国際大学子ども食堂の学生主体の取り組みを報告し、考察を行った。その結果、学生は、子ども食堂ボランティア活動に対して内的動機を持って参加しており、自発的な動きがみられた。また、学生の活動を後押しするものとしては、勉強会があり、活動の意味や専門性を引き出した。さらに、長崎国際大学子ども食堂の活動は、多職種連携教育の場としての可能性が示唆された。

In this study, time-of-flight (TOF) neutron diffraction images of a β-Sn single crystal and a coarse-grained polycrystalline steel plate were obtained using a high-resolution wavelength-shifting fiber based scintillator detector. An inhomogeneous intensity distribution of the 200 reflection from the β-Sn single crystal indicated a large defect density near the surface of the crystal. In addition, the diffraction spots from the individual grains of the steel plate were successfully observed separately in both the normal and width directions. This imaging technique has the potential to be used for evaluating the distribution of material characteristics in different regions inside bulk materials.

Objective It remains unclear whether human T-cell leukemia virus type 1 (HTLV-1) infection influences therapeutic responses in patients with rheumatic diseases and whether immunosuppressive treatments increase the risk of HTLV-1-related complications in HTLV-1 carriers with rheumatic diseases. We examined the effects of tocilizumab (TCZ), an interleukin (IL)-6 receptor antagonist, on two HTLV-1-infected T-cell lines (HCT-5 and MT-2) in vitro. Methods We evaluated production of cytokines and chemokines, expression of HTLV-I associated genes, HTLV-1 proviral load (PVL), expression of HTLV-1 structural proteins, and apoptosis. Results There were no significant differences in cytokine and chemokine levels in the culture supernatants of HCT-5 and MT-2 cells treated with phosphate-buffered saline (PBS) or TCZ. No significant differences were detected in mRNA abundance of Tax or HBZ, PVL, expression of the HTLV-1 structural protein GAG, or apoptosis among HCT-5 and MT-2 cells treated with PBS or TCZ. Conclusions TCZ had no effect the cytokine profiles, HTLV-1 gene and protein expression, PVL, or apoptosis in HTLV-1-infected T-cell lines. Thus, TCZ treatment has no effect on HTLV-1 infection in vitro.

Two-dimensional neutron detectors were developed for the extension of SENJU time-of-flight Laue single crystal neutron diffractometer in J-PARC MLF. The detectors are installed at the additional detector bank for the SENJU instrument. The detector module is made based on ZnS scintillator and wavelength-shifting fiber technology, where each detector module maintains a neutron-sensitive area of 256 × 256 mm with a pixel size of 4 × 4 mm. To meet the tight space limitation in the instrument, the detector was designed as compact as possible. The detector has a depth of 170 mm, which is about 40% smaller than that of the original SENJU detector. Moreover, new comparator electronics cards are implemented, which pick up signals with smaller heights and narrower time widths than the original ones. These cards help decrease in the applied PMT voltage and they improved count uniformity. All four produced detector exhibited similar detector performances: detection efficiency 50-60% for 2-A neutron, 60Co gamma-ray sensitivity 1×10−5, count uniformity 3-6%.

For a radiating charged particle, the radiation reaction force plays an important role in determining its motion. Several formulas have been proposed to describe the radiation reaction force. Stationary solutions of the Lorentz-Abraham-Dirac (LAD), Mo-Papas, Landau-Lifshitz, and Ford-O'Connell equations are obtained and compared for a charged particle under a static magnetic and a rotating electric field. The behaviors of the obtained solutions look quite similar. The relative differences of the Lorentz factor, calculating the values using the LAD equation compared to the other equations, are evaluated; these values are shown to be less than ${10}^{\ensuremath{-}6}$ in the regime where classical radiation reactions are applicable.

Background: Among human T cell leukemia virus type 1 (HTLV-1)-infected individuals, there is an association between HTLV-1 tax subgroups (subgroup-A or subgroup-B) and the risk of HAM/TSP in the Japanese population. To investigate the role of HTLV-1 subgroups in viral pathogenesis, we studied the functional diference in the subgroupspecifc viral transcriptional regulators Tax and HBZ using microarray analysis, reporter gene assays, and evaluation of viral-host protein–protein interaction. Results: (1) Transcriptional changes in Jurkat Tet-On human T-cells that express each subgroup of Tax or HBZ protein under the control of an inducible promoter revealed diferent target gene profles; (2) the number of diferentially regulated genes induced by HBZ was 2–3 times higher than that induced by Tax; (3) Tax and HBZ induced the expres‑ sion of diferent classes of non-coding RNAs (ncRNAs); (4) the chemokine CXCL10, which has been proposed as a prognostic biomarker for HAM/TSP, was more efciently induced by subgroup-A Tax (Tax-A) than subgroup-B Tax (Tax-B), in vitro as well as in unmanipulated (ex vivo) PBMCs obtained from HAM/TSP patients; (5) reporter gene assays indicated that although transient Tax expression in an HTLV-1-negative human T-cell line activated the CXCL10 gene promoter through the NF-κB pathway, there was no diference in the ability of each subgroup of Tax to activate the CXCL10 promoter; however, (6) chromatin immunoprecipitation assays showed that the ternary complex containing Tax-A is more efciently recruited onto the promoter region of CXCL10, which contains two NF-κB binding sites, than that containing Tax-B. Conclusions: Our results indicate that diferent HTLV-1 subgroups are characterized by diferent patterns of host gene expression. Diferential expression of pathogenesis-related genes by subgroup-specifc Tax or HBZ may be asso‑ ciated with the onset of HAM/TSP., 論文

The main clinical feature of human T cell leukemia virus-1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is slowly progressive spastic paraparesis with bladder dysfunction. HAM/TSP is induced by chronic inflammation in the spinal cord, mainly the lower thoracic cord. A long-standing bystander mechanism, such as the destruction of surrounding tissues by the interaction between infiltrated Th1-like, HTLV-1-infected CD4+ T cells and HTLV-1-specific CD8+ cytotoxic T cells (CTL), is probably critical for the induction of chronic inflammation. Although the HTLV-1-infected CD4+ T cells in HAM/TSP appear to play a crucial role in the initial pathogenesis of HAM/TSP, the exact mechanisms of how these cells acquire their function as the first responders in the pathogenesis of HAM/TSP still remain unresolved. Herein, we propose the importance of the activation of both outside-in signals from integrin signaling and inside-out signals for integrin signaling in the HTLV-1-infected CD4+ T cells of HAM/TSP patients.

Immunotherapy using immune checkpoint inhibitors and CAR-T cells has revolutionized treatment for patients with malignant tumors. However, measuring tumor cell cytotoxicity mediated by immune effector cells in clinical laboratories has been difficult due to the requirement for radioactive substances. In this study, a series of novel terpyridine derivative proligands were synthesized, and a non-radioactive cellular cytotoxicity assay using the newly synthesized compounds was developed for use in preclinical and clinical studies for cancer immunotherapy. Once internalized into target cells, the compounds are hydrolyzed by esterases, resulting in the intracellular accumulation of the negatively charged terpyridine derivatives. When the labeled target cells are recognized and killed by immune effector cells, the integrity of the cell membrane is disrupted, and the terpyridine derivatives are released. Upon combining the culture supernatant with europium (Eu3+), the cytotoxicity of immune effector cells for the target cells can be quantitatively determined by measuring the intensity of the Eu3+/ligand-derived time-resolved fluorescence. Thus, the assay developed in this study would facilitate the development of novel cancer immunotherapies., ChemMedChem, 12(23), pp.2006-2013; 2017

Adult T-cell leukemia/lymphoma (ATLL) originates from human T-cell leukemia virus type 1 (HTLV-1) infection due to the activation of the nuclear factor-κB (NF-κB) signaling pathway to maintain proliferation and survival. An important mechanism of the activated NF-κB signaling pathway in ATLL is the activation of the macroautophagy (herafter referred to as autophagy in the remainder of this manuscript)-lysosomal degradation of p47 (NSFL1C), a negative regulator of the NF-κB pathway. Therefore, we considered the use of chloroquine (CQ) or hydroxychloroquine (HCQ) (CQ/HCQ) as an autophagy inhibitor to treat ATLL; these drugs were originally approved by the FDA as antimalarial drugs and have recently been used to treat autoimmune diseases, such as systemic lupus erythematosus (SLE). In this paper, we determined the therapeutic efficacy of CQ/HCQ, as NF-κB inhibitors, in ATLL mediated by blockade of p47 degradation. Administration of CQ/HCQ to ATLL cell lines and primary ATLL cells induced cell growth inhibition in a dose-dependent manner, and the majority of cells underwent apoptosis after CQ administration. As to the molecular mechanism, autophagy was inhibited in CQ-treated ATLL cells, and activation of the NF-κB pathway was suppressed with the restoration of the p47 level. When the antitumor effect of CQ/HCQ was examined using immunodeficient mice transplanted with ATLL cell lines, CQ/HCQ significantly suppressed tumor growth and improved the survival rate in the ATLL xenograft mouse model. Importantly, HCQ selectively induced ATLL cell death in the ATLL xenograft mouse model at the dose used to treat SLE. Taken together, our results suggest that the inhibition of autophagy by CQ/HCQ may become a novel and effective strategy for the treatment of ATLL.

The gustatory system of the sea catfish Plotosus japonicus, like that of other catfishes, is highly developed. To clarify the details of the morphology of the peripheral gustatory system of Plotosus, we used whole-mount immunohistochemistry to investigate the distribution and innervation of the taste buds within multiple organs including the barbels, oropharyngeal cavity, fins (pectoral, dorsal, and caudal), and trunk. Labeled taste buds could be observed in all the organs examined. The density of the taste buds was higher along the leading edges of the barbels and fins; this likely increases the chance of detecting food. In all the fins, the taste buds were distributed in linear arrays parallel to the fin rays. Labeling of nerve fibers by anti-acetylated tubulin antibody showed that the taste buds within each sensory field are innervated in different ways. In the barbels, large nerve bundles run along the length of the organ, with fascicles branching off to innervate polygonally organized groups of taste buds. In the fins, nerve bundles run along the axis of fin rays to innervate taste buds lying in a line. In each case, small fascicles of fibers branch from large bundles and terminate within the basal portions of the taste buds. Serotonin immunohistochemistry demonstrated that most of the taste buds in all the organs examined contained disk-shaped serotonin-immunopositive cells in their basal region. This indicates a similar organization of the taste buds, in terms of the existence of serotonin-immunopositive basal cells, across the different sensory fields in this species.

A large area, position-sensitive scintillation neutron detector was developed for upgrading the SENJU, a time-of-flight Laue single crystal neutron diffractometer, in J-PARC MLF. The detector has a neutron-sensitive area of 512 × 512 mm with a pixel size of 4 × 4 mm. The detector is to be installed below the new vacuum tank to enlarge its scattering angle coverage. A 6Li:ZnS (Ag) scintillator and wavelength-shifting fiber technology is employed to make the prototype detector. Each fiber channel is read out individually with a photon counting method. Detector electronics boards are implemented at the backside of the detector. This configuration enables the detector depth as short as 200 mm. The detector exhibits a detection efficiency of 45% for 1.8-A neutron. No degradation has been observed both in the fiber position and in the neutron sensitivity over one year after the detector assembly. The detector design and its performances are presented.

A real-time data display and storage device was developed for neutron scattering experiments. The device contains two sets of field programmable gate arrays and onboard microcomputers for data display and storage. The developed device can determine the time-of-flight and time- resolved neutron position data with a time range from 0 to 40 ms using a beam of pulsed neutrons at 25 Hz. It was confirmed by an operation test using burst and continuous test pulses that the device exhibited a pulse pair resolution of less than 1 μs and a counting rate capability of more than 1 Mcps.

Objective We investigated the relationships between the efficiency of intercellular transmission of human T-lymphotropic virus type I (HTLV-I) and C-X-C chemokine receptor type 4 (CXCR4) signaling in a comparative study of HTLV-I-infected T cell lines derived from an HTLV-I-associated myelopathy/tropical spastic paraparesis patient (HCT-5) or an HTLV-I carrier (TL-Su). Methods After co-cultivation of each HTLV-I-infected T cell line with H9/K30 luc reporter cells, relative activities of luc were calculated to measure the intercellular transmission of HTLV-I. The level of stromal cell-derived factor-1α was measured using an enzyme-linked immunoassay. Rap1 activation in HTLV-I-infected T cell lines was analyzed by a pull-down assay. Results HCT-5 had higher intercellular transmission efficiency of HTLV-I compared with TL-Su. Intercellular transmission of HTLV-I in TL-Su was increased significantly by stromal cell-derived factor-1α treatment. Pretreatment with an anti-CXCR4 blocking antibody for H9/K30 luc reporter cells induced a significant reduction in intercellular transmission of HTLV-I in HCT-5, but not in TL-Su. Stromal cell-derived factor-1α was not detected in the culture supernatants of HCT-5, but existence of a humoral factor that activates CXCR4 signaling in HCT-5 was suggested from studies with condition media. Bound Rap1-GTP was detected in HCT-5, but not in TL-Su. Conclusions Our data suggest that CXCR4 signaling is involved in the efficiency of intercellular transmission of HTLV-I.

A two-dimensional scintillation neutron detector with a submillimeter spatial resolution was developed for time-of-flight neutron diffraction imaging in the J-PARC MLF. The detector comprised the thin, single ZnS/6LiF scintillator screen coupled with the crossed wavelength -shifting fiber array for light collection. For a high spatial resolution, the wavelength-shifting fibers with a diameter of 0.1 mm were used for assembling the light collection head. The prototype detector that has a neutron-sensitive area of 24 × 24 mm2 exhibited a spatial resolution of 0.20 ± 0.06 mm and 0.16 ± 0.06 mm for x and y directions, respectively. The detector had a detection efficiency of 7% for thermal neutron with a 60Co gamma-ray sensitivity in the order of 10-6. In this paper detector design and specifications are described together with experimental results using the pulsed neutron beam.

Influence of epidemiology and ethnicity on systemic expression of primary Sjogren syndrome in 9974 patients

Objectives To take a “high-definition” picture of the main features of primary Sjogren syndrome (SjS) following a worldwide data-sharing cooperative merging of international clinical SjS databases. Methods The Big Data Sjogren Project Consortium is an international, multicentre registry created in 2014 including leading clinical centres in SjS of the 5 continents that shared a harmonised data architecture and conducted cooperative online efforts to refine collected data of primary SjS patients fulfilling the 2002 classification criteria. Results By January 2018, the participant centres had included 10 475 patients from 22 countries, including 7637 (73%) patients from Europe, 1420 (14%) from America, 1186 (11%) from Asia, 167 (1.4%) from Australia and 65 (0.6%) from Africa. The cohort included 9781 (93%) women and 694 (7%) men, with a mean age at diagnosis of primary SjS of 53 years. The frequencies of fulfilment of the 2002 criteria were 92% for dry eye, 94% for dry mouth, 83% for abnormal ocular tests, 82% for positive minor salivary gland biopsy, 78% for abnormal oral diagnostic tests and 76% for positive anti-Ro/La antibodies. The frequency of positive immunological markers at diagnosis was 79% for ANA, 73% for anti-Ro, 49% for RF, 45% for anti-La, 13% for low C3 levels, 14% for low C4 levels and 7% for cryoglobulins. Conclusions International data sharing-based projects merging disperse clinical registries may be essential tools to increase current knowledge and to improve patient care in specific systemic autoimmune diseases. Disclosure of Interest None declared

The main clinical feature of human T cell leukemia virus-1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is slowly progressive spastic paraparesis with bladder dysfunction. HAM/TSP is induced by chronic inflammation in the spinal cord, mainly the lower thoracic cord. A long-standing bystander mechanism, such as the destruction of surrounding tissues by the interaction between infiltrated Th1-like, HTLV-1-infected CD4

A huge number of neutrinos emitted in core-collapse supernova explosions (ν process) play an important role in stellar nucleosynthesis of some rare nuclides. The study of the neutrino process can contribute to estimation of neutrino energy spectra and explosion mechanism. In the mass region heavier than iron, only three nuclides are known as the neutrino isotopes. If we can find other candidates for neutrino production, it helps to constrain precisely the neutrino energy spectra emitted from proto-neutron stars. A key input for the calculation of the neutrino process is destruction rates by photodisintegration reactions on excited nuclei at high temperature environments. We have proposed direct measurements of photon-induced reaction cross sections on nuclei excited by high power laser to simulate stellar environments.

Objectives To analyse the influence of geolocation on the clinical systemic presentation of primary Sjogren syndrome (SjS) at diagnosis. Methods The Big Data Sjogren Project Consortium is an international, multicentre registry created in 2014. Centres were classified by continent, with an additional north-south sub-classification according to latitude (>or or or Results The highest baseline ESSDAI scores were reported from Southern vs Northern countries in Europe (7.2 vs 4.6, p Conclusions This study provides the first evidence for a strong influence of geolocation on the systemic phenotype of primary SjS at diagnosis. Geographical determinants should be considered as key variables when systemic disease is scored. Disclosure of Interest None declared

To detect HTLV-I bZIP factor (HBZ), tax and relevant molecules in labial salivary glands (LSGs) from patients with Sjögren's syndrome (SS).The expressions of HBZ and tax in T cell lines and LSGs were analysed by in situ hybridization (ISH) or real time PCR. The expressions of forkhead box P3 (Foxp3) and p65 in immunohistochemistry were quantified.After specificity of ISH probes was determined in 5 T cell lines, in LSGs from an adult T-cell leukemia (ATL) patient and 3 HTLV-I-associated myelopathy (HAM)-SS patients, both HBZ and tax signals were detected in infiltrating mononuclear cells (MNCs) and ducts, and HBZ and tax were dominantly expressed in MNCs of ATL and HAM-SS, respectively. HBZ was dominantly observed in LSGs from 8 HTLV-I asymptomatic carrier (AC)-SS patients; faint expression of HBZ was observed in LSGs from 5 HTLV-I-seronegative SS patients. No cell adhesion molecule 1(CADM1) expressed in LSGs from the ATL patient. Although Foxp3 expression was observed in LSG MNCs of all of the SS patients, the ATL patient's expression was significantly greater than that of the AC-SS (p0.01) and HTLV-I-seronegative SS (p0.01) patients. The Foxp3 expression was similar in ATL and HAMSS, but significantly higher in HAM-SS than AC-SS (p0.05). p65 was expressed in LSG MNC nuclei from all SS patients and co-expressed with Foxp3. The expressions of Foxp3 in ducts differed according to HTLV-I infection.These results suggest that HBZ-mediated Foxp3 expression is partly associated with the pathogenesis of HTLV-I-seropositive SS.

The light transport properties of scintillator light inside alternative He-3 neutron detectors using scintillator sheets have been investigated by a ray-tracing simulation code. The detector consists of a light-reflecting tube, a thin rectangular ceramic scintillator sheet laminated on a glass plate, and two photo-multiplier tubes (PMTs) mounted at both ends of the detector tube. The flashes of light induced on the surface of the scintillator sheet via nuclear interaction between the scintillator and neutrons are detected by the two PMTs. The light output at both ends of various detectors in which the scintillator sheets are installed with several different arrangements were examined and evaluated in comparison with experimental results. The results derived from the simulation reveal that the light transport property is strongly dependent on the arrangement of the scintillator sheet inside the tube and the shape of the tube.

A novel ceramic-insulated detector element was developed for two-dimensional neutron measurement, and an irradiation experiment was performed using a Cf-252 neutron source. The element consisted of a ceramic insulator and a ball-shaped anode. It is estimated that a ceramic insulator can suppress the background noise caused by unintentionally scattered neutrons. An electrical field of 1.60×107 V/m was obtained based on a calculation at the top of the ball-shaped anode. Neutron signals were clearly observed using the detector element, thus validating its operation.

Objective To investigate whether human T lymphotropic virus type I (HTLV-I) directly infects salivary gland epithelial cells (SGECs) and induces the niche of the salivary glands in patients with Sjogren's syndrome (SS). Methods SGECs were cultured with the HTLV-I–producing CD4+ T cell line HCT-5 or with Jurkat cells. Antibody arrays, immunofluorescence analysis, and enzyme-linked immunosorbent assay (ELISA) were used to determine the profiles of inflammation-related molecules, and the profiles of apoptosis-related molecules were determined by antibody array and immunofluorescence analysis. The presence of HTLV-I–related molecules was assessed by immunofluorescence analysis and in situ polymerase chain reaction. Apoptosis of SGECs was evaluated by TUNEL staining. Results Among the SGECs, 7.8 ± 1.3% (mean ± SD) were positive for HTLV-I–related proteins after 96-hour coculture with HCT-5 cells. Nuclear NF-κB p65 was also detected in 10% of the SGECs. The presence of HTLV-I proviral DNA in SGECs after coculture with HCT-5 cells was detected by in situ polymerase chain reaction. After coculture of SGECs with HCT-5, the expression of cytokines and chemokines, including soluble intercellular adhesion molecule 1, RANTES, and interferon γ–induced protein 10 kd (IP-10/CXCL10) was increased in a time-dependent manner. The expression of proapoptotic molecules (e.g., cytochrome c and Fas) and antiapoptotic molecules (e.g., Bcl-2, Heme oxygenase 2, and Hsp27) was increased in the SGECs cocultured with HCT-5, showing that apoptosis of SGECs was not detected after coculture with HCT-5 or Jurkat cells. Conclusion HTLV-I is thought to infect SGECs and alter their cellular functions. These changes may induce the niche of SS and contribute to the development of SS in anti–HTLV-I antibody–positive individuals.

When intense laser beams interact with solid targets, high-energy photons are effectively generated via radiation reaction effect. These photons receive a large portion of the incident laser energy, and the energy transport by photons through the target is crucial for the understanding of the laser–matter interactions. In order to understand the energy transport, we newly developed a Particle-in-Cell code which includes the photon–matter interactions by introducing photon macro-particles. Test simulations are performed and compared with simulations using a particle transport code, which shows a good agreement.

Progress in laser physics enabled us to produce various quantum beams from high field plasma generated from the interaction between high peak power laser and materials. We have proposed the nuclear astrophysics experiments using gamma-ray pulses generated by the high peak power laser.

Baseline Essdai/ Das Scores In 8061 Patients With Primary Sjogren Syndrome : Characterization Of Systemic Disease

Objectives Baseline characterization of European patients diagnosed with primary Sjogren syndrome (SS) according to the 2002 AE criteria. Methods The Big Data Sjogren Project was formed in 2014 to take a “high-definition” picture of the main features of primary SS by merging international SS databases. International experts of the EULAR-SS Task Force were invited to participate. By January 2017, the database included 9302 consecutive patients recruited from 21 countries of the 5 continents. Results A total of 6586 (71%) patients were included from European countries. In comparison with non-European countries, European patients had a higher mean age (54 v 51yrs, p Conclusions European patients are diagnosed at older age, are more frequently men, and presented a lower frequency of anti-Ro/La antibodies and a higher frequency of immunological markers related to mixed cryoglobulinemia. Disclosure of Interest None declared

Millions of people are infected with human T-lymphotropic virus type 1 (HTLV-1) worldwide; notable endemic areas include Brazil, the Caribbean islands, Iran, and Japan. A small number of those infected develop the progressive neurodegenerative disease HTLV-1-associated myelopathy (HAM), also known as tropical spastic paraparesis (TSP), which is characterized by chronic spinal cord inflammation and accompanying myelopathic symptoms. The corticosteroid prednisolone (PSL) is a classic treatment for HAM/TSP, yet its effectiveness remains controversial owing to insufficient and conflicting studies. We conducted a multicenter retrospective study using data collected by physicians monitoring patients with HAM/TSP at 7 hospitals throughout Japan. The Osame Motor Disability Score (OMDS) was used to evaluate 57 patients treated with low-dose PSL (mean 4.8 mg/day) versus 29 untreated patients. Roughly half of the evaluations spanned < 3 years (Short-Term) and half > 3 years (Long-Term), with a mean of 3.4 years. While the OMDS of most untreated patients remained unchanged in the Short-Term (87%) and worsened in the Long-Term (79%), most treated patients improved in the Short-Term (52%) and remained unchanged or improved in the Long-Term (68%). Overall, the mean change in OMDS per year was –0.13 in the Steroids group and +0.12 in the Untreated group (p < 0.01). This study addressed the effectiveness of PSL for HAM/TSP in 3 novel ways: 1) continuous low-dose administration; 2) comparison with an untreated group; and 3) Long-Term evaluation. These findings provide robust evidence supporting PSL maintenance therapy for HAM/TSP.

We propose nuclear experiments using γ-ray pulses provided from high field plasma generated by high peak power laser. These γ-ray pulses have the excellent features of extremely short pulse, high intensity, and continuous energy distribution. These features are suitable for the study of explosive nucleosyntheses in novae and supernovae, such as the γ process and ν process. We discuss how to generate suitable γ-ray pulses and the nuclear astrophysics involved.

Objectives To evaluate oral prosultiamine treatment in patients with overactive bladder accompanied by human T-lymphotropic virus type 1-associated myelopathy/tropical spastic paraparesis. Methods This was a prospective, single-center, open-label study. Patients received oral prosultiamine (300 mg) once daily in the morning, and the overactive bladder symptom score and urine levels of overactive bladder-related biomarkers (nerve growth factor/creatinine and adenosine triphosphate/creatinine) 12 weeks after the initial administration were compared with the baseline values. In addition, the urodynamic parameters, including involuntary detrusor contraction and detrusor sphincter dyssynergia, were evaluated before and after treatment. Results A total of 16 patients were recruited for this clinical study. In the overactive bladder symptom score, night-time frequency, urgency and the total score improved after oral prosultiamine treatment (P = 0.028, 0.001 and 0.004, respectively). Both urinary nerve growth factor/creatinine and adenosine triphosphate/creatinine levels decreased significantly after the treatment (P = 0.004 and 0.017, respectively). Urodynamic studies showed that the maximum cystometric capacity increased significantly after the treatment. However, the symptoms disappeared because of the treatment in six of 10 patients with involuntary detrusor contraction (60%) and three of seven patients with detrusor sphincter dyssynergia (42.9%). There were no serious adverse events. Conclusions The changes in urodynamic parameters and urine levels of overactive bladder-related markers suggest that oral prosultiamine is a safe and effective treatment for overactive bladder with human T-lymphotropic virus type 1-associated myelopathy/tropical spastic paraparesis.

A neutron-sensitive ZnS/10B2O3 ceramic scintillator detector was developed as an alternative to a 3He-gas-based detector for use in a plutonium canister assay system. The detector has a modular structure, with a flat ZnS/10B2O3 ceramic scintillator strip that is installed diagonally inside a light-reflecting aluminium case with a square cross-section, and where the scintillation light is detected using two photomultiplier tubes attached at both ends of the case. The prototype detectors, which have a neutron-sensitive area of 30 mm×250 mm, exhibited a sensitivity of 21.7–23.4±0.1 cps/nv (mean±SD) for thermal neutrons, a 137Cs gamma-ray sensitivity of 1.1–1.9±0.2×10−7 and a count variation of less than 6% over the detector length. A trial experiment revealed a temperature coefficient of less than −0.24±0.05%/°C over the temperature range of 20–50 °C. The detector design and the experimental results are presented.

Objective To investigate the relationship between the intercellular transmission efficiency of human T-lymphotropic virus type I (HTLV-I) and the signaling involved in actin polymerization during cytoskeletal reorganization in a comparative study of HTLV-I-infected T-cell lines derived from an HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patient or an HTLV-I carrier. Methods HCT-5 and TL-Su cells derived from an HAM/TSP patient and an HTLV-I carrier, respectively, were used as HTLV-I-infected T-cell lines. After co-cultivation of each HTLV-I-infected T-cell line with H9/K30 luc reporter cells, the relative luc activities were calculated to analyze the efficiency of intercellular transmission of HTLV-I. The intracellular levels of cyclic adenosine monophosphate (cAMP) or cyclic guanosine monophosphate (cGMP) were measured in enzyme-linked immunoassays. The expression of phosphorylated vasodilator-stimulated phosphoprotein (p-VASP) was analyzed by western blotting. Results Treatment of HCT-5 cells with latrunculin B, an inhibitor of actin polymerization, significantly suppressed the relative luc activity. Western blotting analysis of HCT-5 cells treated with the adenylyl cyclase activator forskolin showed upregulation of p-VASP, with a concomitant and significant increase in the intracellular cAMP concentration. Furthermore, the relative luc activity was significantly decreased. The intracellular cAMP, but not cGMP levels, were significantly lower in HCT-5 than in TL-Su. Vasodilator-stimulated phosphoprotein appeared less phosphorylated in HCT-5 than in TL-Su. The relative luc activity was significantly higher in HCT-5 than in TL-Su. Conclusions The intracellular cAMP concentration regulates the efficiency of intercellular HTLV-I transmission under the control of p-VASP expression, suggesting the intercellular transmission potential of HTLV-I-infected T cells of HAM/TSP patients is enhanced by downregulated intracellular cAMP levels., Clinical and Experimental Neuroimmunology, 5(2), pp.209-215; 2014

The main therapeutic strategy against human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) characterized by lower extremity motor dysfunction is immunomodulatory treatment, with drugs such as corticosteroid hormone and interferon-α, at present. However, there are many issues in long-term treatment with these drugs, such as insufficient effects and various side effects. We now urgently need to develop other therapeutic strategies. The heparinoid, pentosan polysulfate sodium (PPS), has been safely used in Europe for the past 50 years as a thrombosis prophylaxis and for the treatment of phlebitis. We conducted a clinical trial to test the effect of subcutaneous administration of PPS in 12 patients with HAM/TSP in an open-labeled design. There was a marked improvement in lower extremity motor function, based on reduced spasticity, such as a reduced time required for walking 10 m and descending a flight of stairs. There were no significant changes in HTLV-I proviral copy numbers in peripheral blood contrary to the inhibitory effect of PPS in vitro for intercellular spread of HTLV-I. However, serum soluble vascular cell adhesion molecule (sVCAM)-1 was significantly increased without significant changes of serum level of chemokines (CXCL10 and CCL2). There was a positive correlation between increased sVCAM-1and reduced time required for walking 10 m. PPS might induce neurological improvement by inhibition of chronic inflammation in the spinal cord, through blocking the adhesion cascade by increasing serum sVCAM-1, in addition to rheological improvement of the microcirculation. PPS has the potential to be a new therapeutic tool for HAM/TSP.

A position-sensitive tubular scintillator-based neutron detector is proposed as an alternative to a 3 He-gas-based detector. The detector has a neutron-detecting element constructed from rolled ZnS/ 6 LiF scintillator screens that sandwich wavelength-shifting (WLS) fibre coils (SFC element). Multiple SFC elements are enclosed in an aluminium tube in a row to form a one-dimensional position-sensitive neutron detector. The design of the WLS fibre coil, which was determined by performing basic experiments, comprised two 0.75-mm-diameter WLS fibres wound in parallel at a pitch of 1.5 mm. A 64-element detector with a pixel size of 22 mm×20 mm (width×length) successfully demonstrated the detection principle. The tubular shape of the new detector is similar to the usual 25-mm-diameter 3 He tube, making this an alternative detector with the potential to be installed in a vacuum tank for inelastic-neutron-scattering instruments.

A scintillator-based neutron-counting imaging detector with a sub-100-μm spatial resolution was developed for energy-selective neutron imaging. The detector head of the detector comprised a thin ZnS/6LiF scintillator screen, a fibre-optic taper and crossed wavelength-shifting (WLS) fibre arrays. A high spatial resolution was achieved by constructing the scintillator with a thickness of 100 μm and placing it in contact with the fibre-optic taper at a magnification ratio of 3.1:1. WLS fibres with a diameter of 100±5 μm (mean±SD) were specially made, and their dye content was optimized for use in crossed WLS-fibre arrays. The developed detector had a pixel size of 34 μm×34 μm, and exhibited spatial FWHM resolutions of 80±7 μm and 61±6 μm in the x and y directions, respectively. A small prototype detector demonstrated the capability of neutron imaging using Bragg edges of a Cu/Fe sample when using the pulsed-neutron source in the Materials and Life Science Experimental Facility at the Japan Proton Accelerator Research Complex.